PMID- 22118463
OWN - NLM
STAT- MEDLINE
DCOM- 20120123
LR  - 20220408
IS  - 1097-4172 (Electronic)
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 147
IP  - 5
DP  - 2011 Nov 23
TI  - Lin28A and Lin28B inhibit let-7 microRNA biogenesis by distinct mechanisms.
PG  - 1066-79
LID - 10.1016/j.cell.2011.10.039 [doi]
AB  - Lin28A and Lin28B selectively block the expression of let-7 microRNAs and 
      function as oncogenes in a variety of human cancers. Lin28A recruits a TUTase 
      (Zcchc11/TUT4) to let-7 precursors to block processing by Dicer in the cell 
      cytoplasm. Here we find that unlike Lin28A, Lin28B represses let-7 processing 
      through a Zcchc11-independent mechanism. Lin28B functions in the nucleus by 
      sequestering primary let-7 transcripts and inhibiting their processing by the 
      Microprocessor. The inhibitory effects of Zcchc11 depletion on the tumorigenic 
      capacity and metastatic potential of human cancer cells and xenografts are 
      restricted to Lin28A-expressing tumors. Furthermore, the majority of human colon 
      and breast tumors analyzed exclusively express either Lin28A or Lin28B. Lin28A is 
      expressed in HER2-overexpressing breast tumors, whereas Lin28B expression 
      characterizes triple-negative breast tumors. Overall our results illuminate the 
      distinct mechanisms by which Lin28A and Lin28B function and have implications for 
      the development of new strategies for cancer therapy.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Piskounova, Elena
AU  - Piskounova E
AD  - Stem Cell Program, Children's Hospital, Boston, MA 02115, USA.
FAU - Polytarchou, Christos
AU  - Polytarchou C
FAU - Thornton, James E
AU  - Thornton JE
FAU - LaPierre, Robert J
AU  - LaPierre RJ
FAU - Pothoulakis, Charalabos
AU  - Pothoulakis C
FAU - Hagan, John P
AU  - Hagan JP
FAU - Iliopoulos, Dimitrios
AU  - Iliopoulos D
FAU - Gregory, Richard I
AU  - Gregory RI
LA  - eng
GR  - R01 GM086386/GM/NIGMS NIH HHS/United States
GR  - R01 GM086386-01A1/GM/NIGMS NIH HHS/United States
GR  - 1R01GM086386-01A1/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (LIN28B protein, human)
RN  - 0 (Lin28A protein, human)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (TUT4 protein, human)
RN  - 0 (mirnlet7 microRNA, human)
SB  - IM
MH  - Amino Acid Sequence
MH  - Breast Neoplasms/*genetics/pathology
MH  - Cell Nucleolus/metabolism
MH  - Cell Nucleus/metabolism
MH  - Colonic Neoplasms/*genetics/pathology
MH  - DNA-Binding Proteins/*metabolism
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - MicroRNAs/*genetics
MH  - Molecular Sequence Data
MH  - Neoplasm Invasiveness
MH  - RNA-Binding Proteins/chemistry/*genetics
MH  - Transcription, Genetic
PMC - PMC3227872
MID - NIHMS336756
EDAT- 2011/11/29 06:00
MHDA- 2012/01/24 06:00
PMCR- 2012/11/23
CRDT- 2011/11/29 06:00
PHST- 2011/03/08 00:00 [received]
PHST- 2011/07/25 00:00 [revised]
PHST- 2011/10/24 00:00 [accepted]
PHST- 2011/11/29 06:00 [entrez]
PHST- 2011/11/29 06:00 [pubmed]
PHST- 2012/01/24 06:00 [medline]
PHST- 2012/11/23 00:00 [pmc-release]
AID - S0092-8674(11)01289-X [pii]
AID - 10.1016/j.cell.2011.10.039 [doi]
PST - ppublish
SO  - Cell. 2011 Nov 23;147(5):1066-79. doi: 10.1016/j.cell.2011.10.039.